Curiosity & Collaboration: The Work of Michael Potter (1924–2013)

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Plasma Cell Tumor Development: A Complex Multi-Step Process

What Causes Cancer?

Potter now knew a great deal about immunoglobulins. He knew that they are antibodies that bind to antigens. He knew each one attaches to only one kind of antigen. He knew their three-dimensional structure and basic genetic composition. But there was one question that he still could not answer: Why were the BALB/cAn mice the only ones that developed plasma cell tumors when injected with mineral oil or plastic shavings? In other words, what caused the tumors to develop? The answer would open new fields in cancer and immunology.

“He tirelessly examined tens of thousands of stained tumor slides. Towers of stacked slideboxes teetered around him and occasionally came crashing down.”
—Gary Jones, NCI

Olympus Compound Microscope

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Micrograph of Plasma Cells

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National Library of Medicine. Learn more about Potter's Olympus Microscope (TODO: Link)

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Michael Potter's Microscope

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Permanent collection of the NIH Stetten Museum. Courtesy of Dr. Beverly Mock, NCI

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National Library of Medicine

Potter was usually at his laboratory bench using this microscope. Shown are plasma cells with darkly stained nuclei. The clear spots next to the nucleus are perinuclear “hoffs” and are filled with newly synthesized protein, in this case, antibody.

Retroviruses Oncogene Activation

Potter collaborated with Marshall Sklar and Wallace Rowe of the National Institute of Allergy and Infectious Diseases to see if viruses could affect the growth of Potter’s plasma cell tumors. Although viruses did not cause the tumors, they found that retroviruses containing oncogenes could accelerate tumor growth when injected into mice, and could even induce tumors in normally resistant mice. Grace Shen-Ong, who worked in Potter’s laboratory, and Michael Cole then found that plasma cells that develop tumors have chromosomal translocations involving genes for immunoglobulins and an oncogene called MYC. But Potter — working with J. Frederic Mushinski, Ken Marcu, Rex Risser, and Siegfried Janz — found that these translocations alone did not cause tumors. And retroviruses had to contain both MYC and another oncogene to induce plasma cell tumors.

Illustration showing oncogene activation causing cells to proliferate

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Illustration designed by Sayeh Gorjifard, NCI, OD, CCT

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Potter and Beverly Mock identified genetically inherited alleles of genes that control the susceptibility of BALB/c mice to plasma cell tumor development. Mock performed one of the first genome-wide linkage studies in mice showing that multiple genes are linked to tumor susceptibility. Then they created congenic strains of mice to fine map the genes to specific regions of chromosomes, leading to the identification of two tumor suppressors (p16 and Mndal) and a growth promoting gene (mTOR) as plasma cell tumor susceptibility genes. BALB/c mice carry a rare allele of mTOR. Today, these tumor incidence studies have been used to inform potential drug combination therapies for people with multiple myeloma.

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Beverly Mock, Ph.D., Senior Investigator, Laboratory of Cancer Biology and Genetics, NCI/CCR

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NCI Collection. Photo by Bill Branson

Creating a New Technique

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Potter wanted to study the early stages of tumor growth, but these tumors only grew in animals. In 1986, Richard Nordan, a graduate student in Potter’s laboratory found that the tumors could be grown in tissue culture, if they were grown in liquids from cultured white blood cells called macrophages. Nordan identified the component in the liquid as interleukin-6, which is involved in the growth and differentiation of normal white blood cells. Potter and Nordan had discovered a way to grow tumors in the laboratory and a new tool for scientists of many specialities.

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National Library of Medicine

Formal Recognition

“Dr. Potter's catalytic influence on the field of antibody research has extended far beyond his own laboratory through his generous sharing of materials, cell lines, information, and creative ideas.”

—Lasker Foundation citation

The Ehrlich Prize

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In 1983, the Paul Ehrlich Foundation awarded the Ehrlich Prize to Potter, Peter Doherty, and Rolf Zinkernagel for their immunological research. Potter had been elected to the National Academy of Sciences in 1981, an award he cherished because it was the result of the recognition of his peers.

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Courtesy of Melissa Adde

Curiosity & Collaboration: The Work of Michael Potter (1924–2013)

Versions Compared

Old Version 9

New Version 10

Key

Plasma Cell Tumor Development: A Complex Multi-Step Process

What Causes Cancer?

Olympus Compound Microscope

Retroviruses Oncogene Activation

Creating a New Technique

Formal Recognition

The Ehrlich Prize

Office of NIH History and Stetten Museum